Silica/organosilica cross-linked block copolymer micelles: a versatile theranostic platform.

As a member of the organic-inorganic hybrid family, silica/organosilica cross-linked block copolymer micelles are becoming increasingly attractive due to the combined features of excellent self-assembly properties of amphiphilic block copolymers and the high stability and the easy surface modification of silica/organosilica components. Compared to the traditional cross-linking route with organic components, the silica/organosilica cross-linking approach could offer more advantages, such as quick reaction under mild conditions, a much stronger barrier to the diffusion of both encapsulated small molecules and functional nanoparticles and the substantial improvement in the stability of the whole micelles against the ambient environment. In this tutorial review, we will focus on the recent developments in the design, synthesis and biomedical applications of silica/organosilica cross-linked block copolymer micelles based on the self-assembly of amphiphilic block copolymers and the hydrolysis and condensation of silanes in aqueous solution. First, we will summarize the synthesis of three typical kinds of silica/organosilica cross-linked block copolymer micelles based on the self-assembly of non-ionic polyethylene oxide (PEO)-based, cationic and anionic poly(acrylic acid) (PAA)-based block copolymer micelles. Then, a series of multifunctional silica/organosilica cross-linked block copolymer micelles by encapsulating various functional nanoparticles/molecules in the hydrophobic polymer cores or hydrophilic silica/organosilica cross-linked shells are introduced and their biomedical applications in controlled drug delivery, bio-imaging (magnetic resonance, fluorescence and multimodal imaging) and imaging-guided therapies (photothermal and high intensity focused ultrasound therapies) will be discussed. Finally, the challenges and prospects of silica/organosilica cross-linked micellar nanostructures and their biological applications are discussed and assessed. It is highly expected that the silica/organosilica cross-linked micelles may provide a new and promising kind of carrier system for enhanced bio-imaging and efficient cancer therapy.

[1]  Cornelus F. van Nostrum,et al.  Covalently cross-linked amphiphilic block copolymer micelles , 2011 .

[2]  Siew Yee Wong,et al.  PEO surface-decorated silica nanocapsules and their application in in vivo imaging of zebrafish , 2012 .

[3]  Weihong Zhu,et al.  A Hydrophobic Dye‐Encapsulated Nano‐Hybrid as an Efficient Fluorescent Probe for Living Cell Imaging , 2012, Advanced healthcare materials.

[4]  Yang Sun,et al.  Superparamagnetic PLGA-iron oxide microcapsules for dual-modality US/MR imaging and high intensity focused US breast cancer ablation. , 2012, Biomaterials.

[5]  Yuanyi Zheng,et al.  Facile Synthesis of Magnetite/Perfluorocarbon Co‐Loaded Organic/Inorganic Hybrid Vesicles for Dual‐Modality Ultrasound/Magnetic Resonance Imaging and Imaging‐Guided High‐Intensity Focused Ultrasound Ablation , 2013, Advanced materials.

[6]  Andrew L. Ferguson,et al.  Investigating the optimal size of anticancer nanomedicine , 2014, Proceedings of the National Academy of Sciences.

[7]  Siew Yee Wong,et al.  PEOlated Micelle/Silica as Dual-Layer Protection of Quantum Dots for Stable and Targeted Bioimaging , 2013 .

[8]  A. Eisenberg,et al.  Control of amphiphilic block copolymer morphologies using solution conditions , 2003, The European physical journal. E, Soft matter.

[9]  Luis M Liz-Marzán,et al.  Recent Progress on Silica Coating of Nanoparticles and Related Nanomaterials , 2010, Advanced materials.

[10]  Qiaoling Zhao,et al.  A facile approach to fabricate functionalized superparamagnetic copolymer-silica nanocomposite spheres. , 2008, Chemical communications.

[11]  Siew Yee Wong,et al.  Silica-F127 nanohybrid-encapsulated manganese oxide nanoparticles for optimized T1 magnetic resonance relaxivity. , 2014, Nanoscale.

[12]  Xiaohan Liu,et al.  Controlled synthesis of shell cross-linked magnetic micelles for efficient liver MR imaging , 2012 .

[13]  H. Tian,et al.  Morphology‐Tailoring of a Red AIEgen from Microsized Rods to Nanospheres for Tumor‐Targeted Bioimaging , 2016, Advanced materials.

[14]  Yanli Zhao,et al.  Silica–Polymer Hybrid with Self‐Assembled PEG Corona Excreted Rapidly via a Hepatobiliary Route , 2016 .

[15]  Siew Yee Wong,et al.  Facile synthesis of hybrid silica nanocapsules by interfacial templating condensation and their application in fluorescence imaging. , 2009, Chemical communications.

[16]  J. Ding,et al.  A new family of biocompatible and stable magnetic nanoparticles: silica cross-linked pluronic F127 micelles loaded with iron oxides , 2009 .

[17]  Xiaohan Liu,et al.  Facile Synthesis of Monodisperse Superparamagnetic Fe3O4 Core@hybrid@Au Shell Nanocomposite for Bimodal Imaging and Photothermal Therapy , 2011, Advanced materials.

[18]  D. Zhao,et al.  Ordered mesoporous silicas and carbons with large accessible pores templated from amphiphilic diblock copolymer poly(ethylene oxide)-b-polystyrene. , 2007, Journal of the American Chemical Society.

[19]  M Montalti,et al.  Dye-doped silica nanoparticles as luminescent organized systems for nanomedicine. , 2014, Chemical Society reviews.

[20]  Siew Yee Wong,et al.  A Hybrid Silica Nanoreactor Framework for Encapsulation of Hollow Manganese Oxide Nanoparticles of Superior T1 Magnetic Resonance Relaxivity , 2015 .

[21]  Zhi Ma,et al.  Preparation of Uniform, Water‐Soluble, and Multifunctional Nanocomposites with Tunable Sizes , 2010 .

[22]  L. Tang,et al.  Nonporous Silica Nanoparticles for Nanomedicine Application. , 2013, Nano today.

[23]  H. Tian,et al.  A pH-responsive hybrid fluorescent nanoprober for real time cell labeling and endocytosis tracking. , 2013, Biomaterials.

[24]  Jörg Huwyler,et al.  Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[25]  Yingli An,et al.  Facile strategy for synthesis of silica/polymer hybrid hollow nanoparticles with channels. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[26]  Karen L. Wooley,et al.  The Importance of Chemistry in Creating Well-Defined Nanoscopic Embedded Therapeutics: Devices Capable of the Dual Functions of Imaging and Therapy , 2011, Accounts of chemical research.

[27]  Yuanyi Zheng,et al.  Perfluorohexane‐Encapsulated Mesoporous Silica Nanocapsules as Enhancement Agents for Highly Efficient High Intensity Focused Ultrasound (HIFU) , 2012, Advanced materials.

[28]  John Wang,et al.  Silica-based nanocapsules: synthesis, structure control and biomedical applications. , 2015, Chemical Society reviews.

[29]  Jun Liu,et al.  Size-Tunable and Functional Core−Shell Structured Silica Nanoparticles for Drug Release , 2010 .

[30]  Craig J Hawker,et al.  Cross-linked block copolymer micelles: functional nanostructures of great potential and versatility. , 2006, Chemical Society reviews.

[31]  Xiaohan Liu,et al.  Fabrication of uniform, biocompatible and multifunctional PCL-b-PAA copolymer-based hybrid micelles for magnetic resonance imaging , 2011 .

[32]  R. Montis,et al.  Silica-based nanoparticles: a versatile tool for the development of efficient imaging agents. , 2015, Chemical Society reviews.

[33]  M. Kruk,et al.  Single-micelle-templated synthesis of hollow silica nanospheres with tunable pore structures , 2015 .

[34]  K. Wooley,et al.  Polymeric Nanostructures for Imaging and Therapy. , 2015, Chemical reviews.

[35]  Fen Zou,et al.  Folate-decorated PEG-PLGA nanoparticles with silica shells for capecitabine controlled and targeted delivery. , 2014, International journal of pharmaceutics.

[36]  D. Yao,et al.  Different dimensional silica materials prepared using shaped block copolymer nanoobjects as catalytic templates. , 2015, Journal of materials chemistry. B.

[37]  Ling He,et al.  Pyridine-containing block copolymer/silica core-shell nanoparticles for one-step preparation of superhydrophobic surfaces. , 2013, Physical chemistry chemical physics : PCCP.

[38]  F. Kiessling,et al.  Core-Crosslinked Polymeric Micelles: Principles, Preparation, Biomedical Applications and Clinical Translation. , 2015, Nano today.

[39]  Yuanyi Zheng,et al.  A simple route to prepare monodisperse Au NP-decorated, dye-doped, superparamagnetic nanocomposites for optical, MR, and CT trimodal imaging. , 2013, Small.

[40]  Siew Yee Wong,et al.  Silica nanocapsules of fluorescent conjugated polymers and superparamagnetic nanocrystals for dual-mode cellular imaging. , 2011, Chemistry.

[41]  Q. Huo,et al.  Silica cross-linked nanoparticles encapsulating fluorescent conjugated dyes for energy transfer-based white light emission and porphyrin sensing. , 2012, Nanoscale.

[42]  M. Yada,et al.  Synthesis of silica hollow nanoparticles templated by polymeric micelle with core-shell-corona structure. , 2007, Journal of the American Chemical Society.

[43]  S. Armes,et al.  Shell cross-linked micelles as cationic templates for the preparation of silica-coated nanoparticles: strategies for controlling the mean particle diameter. , 2009, Macromolecular rapid communications.

[44]  S. Armes,et al.  Recent advances in shell cross-linked micelles. , 2007, Chemical communications.

[45]  Mithat Gönen,et al.  Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe , 2014, Science Translational Medicine.

[46]  H. Tian,et al.  Constructing NIR silica–cyanine hybrid nanocomposite for bioimaging in vivo: a breakthrough in photo-stability and bright fluorescence with large Stokes shift , 2013 .

[47]  Jun Liu,et al.  A new class of silica cross-linked micellar core-shell nanoparticles. , 2006, Journal of the American Chemical Society.

[48]  Siew Yee Wong,et al.  Silica-shell cross-linked micelles encapsulating fluorescent conjugated polymers for targeted cellular imaging. , 2012, Biomaterials.

[49]  S. Armes,et al.  Cross-linking of cationic block copolymer micelles by silica deposition. , 2007, Journal of the American Chemical Society.

[50]  B. Liu,et al.  Silica shelled and block copolymer encapsulated red-emissive AIE nanoparticles with 50% quantum yield for two-photon excited vascular imaging. , 2015, Chemical communications.

[51]  Jian Liu,et al.  Organic−Inorganic Hybrid Hollow Nanospheres with Microwindows on the Shell , 2008 .

[52]  A. Elaissari,et al.  Silica-based nanoparticles for biomedical applications. , 2012, Drug discovery today.

[53]  J. Xue,et al.  Synthesis of PEOlated Fe3O4@SiO2 Nanoparticles via Bioinspired Silification for Magnetic Resonance Imaging , 2010 .

[54]  W. Stöber,et al.  Controlled growth of monodisperse silica spheres in the micron size range , 1968 .